Blood-Brain Barrier – What Is It?

brain-barrier“Homeostasis” is not a topic commonly discussed at parties or at the dinner table. Nobody pays attention to it unless it’s severely out of order. That’s because few of us know what it is. Your body is able to control everything that goes on inside—the composition of body fluids, the physiological responses to stimuli, the maintenance of body temperature, and whatever else we need to keep equilibrium. That’s homeostasis. Nowhere in the body is it more important than in the brain. The mechanism for supporting this lies in the blood-brain barrier, the BBB. This comprises a network of capillaries that supply blood to the brain. The permeability of these particular capillaries is such that some substances are prevented from entering the brain tissue while others are allowed. Sometimes it’s only a matter of big molecules versus small molecules. The BBB was discovered by a bacteriologist named Paul Ehrlich, who found that a dye injected into the bloodstream colored the tissues of most organs except the brain.

Further study realized that the barrier is located in the endothelial (skin-like) cells of the capillaries, which are joined by tight junctions of substantial electrical resistance, providing a barrier against some molecules. The BBB is both a physical barrier and a system of cellular transport mechanisms. It restricts the passage of potentially harmful materials from the blood, yet allows the traverse of nutrients. Fat-soluble substances, such as ethanol and caffeine, are able to get through by way of the lipid membranes of the cells. Oddly, water-soluble materials, such as sodium and potassium, may not cross the barrier without an escort molecule of some type.

The BBB becomes more permeable during inflammatory attacks, allowing some medications (mostly antibiotics) and phagocytes to pass through. That’s good. A not-so-good thing is that opportunistic bacteria and viruses can get through, too. Most of them are too big, though. Therefore, brain infections are rare. One exception is the spirochete, Borrelia, associated with Lyme’s disease, which seems to be able to infiltrate blood vessel walls after causing inflammation of the central nervous system. (Rupprecht. 2008)  There are very few fat-soluble small molecules that can get through, and that can cause problems when life-saving chemicals are barred entrance. (Pardridge. 2002)  Other than some infectious diseases, no chronic diseases are cured by small-molecule drugs. Large-molecule drugs have the potential to heal patients with neurological conditions, but none can cross the BBB.


What can harm the blood-brain barrier?  Alcohol, fluoride, oxidized LDL and brain concussions, to name a few.  Alcohol crosses the BBB (Stins. 2009) and forms metabolites that act as signaling molecules to activate enzymes leading to BBB dysfunction and to neuro-inflammatory disorders. (Haorah. 2007)  Furthermore, alcohol causes oxidative neuron damage and results in cognitive deficits that characterize stupor and memory lapses, all because it inhibits the glucose transport upon which the brain depends as a source of energy. (Abdul Muneer. 2011)

As beneficial as topical fluoride might be in the prevention of tooth decay, its ingestion is another story, where elevated levels have been associated with increased rates of mental deficiency and borderline intelligence. Chinese researchers found that high fluoride levels in drinking water have a profound effect on the intelligence of developing children. (Xiang. 2003)  Simultaneous study concluded that fluoride accumulates in the hippocampus—the part of the brain involved in memory—and inhibits activity of cholinesterase, the enzyme that regulates the function of the neurotransmitter, acetylcholine, which mediates synaptic activity. (Zhai. 2003)  In earlier investigations, scientists found that the chemical had impact on those persons chronically exposed to industrial fluoride pollution, wherein there occurred symptoms of impaired central nervous system functioning and faulty cognitions and memories. (Spittle. 1994)  From the outside, fluoride is acceptable treatment for the prevention of caries; from the inside, no.

Oxidized LDL (oxLDL), which appears when LDL spends too much time in the blood before getting repackaged as fat by the liver or being taken up by peripheral tissue, is capable of inducing cell injury. When cerebral endothelial cells are exposed to OxLDL, their viability decreases in a concentration- and time-dependent manner, and their programmed cell death is hastened. Intracellular reactive oxygen species are increased, and mitochondria become dysfunctional. (Chen. 2007)  A blow to the head can cause a concussion, but so can violent jarring or shaking. This sudden change of momentum (the resistance to changes in motion or stability) may evoke unconsciousness or disruption of vital functions of the brainstem. The increased pressure that may result will render the BBB increasingly permeable, particularly at the site of insult. (Beaumont. 2001)


Is there a way to protect the BBB?  Yes, but there is space here to address only a few. Caffeine—we all know how to get that—has been shown to block disruption of the blood brain barrier in a rabbit model of Alzheimer’s disease (AD). So, what do rabbits have to do with people?  Lab animals are selected based on their organ systems’ similarity of function to corresponding systems in humans. In a cholesterol-induced model of AD, scientists found that caffeine was able to block substances that compromise the integrity of the molecules (called occludins) that hold the tight junctions of the BBB together. (Chen. 20081)  Perhaps caffeine and related drugs may be useful to treat AD. But there’s more. In Parkinson’s disease (PD), similar BBB disruptions are characteristic, and caffeine again was the rescue agent. (Chen. 20082)  (Chen. 2010)

Indian neurologists have studied the effects of curcumin (from turmeric) on patients with AD, and have found the herb’s anti-oxidant and anti-inflammatory properties to be beneficial in treating dementia and traumatic brain injury. The pharmacological effects of curcumin have decreased beta-amyloid plaques, delayed degradation of neurons, and decreased microglia formation while improving overall memory in AD patients. (Mishra. 2008)

Valproic acid (VPA), a histone deacetylase inhibitor, is a drug used to prevent seizures and to stabilize mood, used mostly in epilepsy treatment. Histone acetylation plays an important role in the regulation of gene expression. Keeping it intact is vital. Valproic acid and others of its kind do just that. It protects against cerebral ischemia (decrease of blood supply) and prevents disruption of the BBB. The effects of VPA are mimicked by a companion molecule, sodium butyrate, a compound available as an OTC supplement. (Wang, et al. 2011)  Inflammation and macrophage infiltration follow a cerebral ischemic attack. Injected sodium butyrate or VPA was found to be effective at reducing the area of infarction and inhibiting inflammatory markers, as long as administration occurred within a three-hour window. The potential for use in stroke patients is being studied. (Kim. 2007)

One of the hottest supplements on the market is resveratrol, the magical ingredient in grapes, peanuts and red wine that purports to protect against aging.  Whether it can do that or not is insignificant in light of its use as an anti-mutagenic, anti-inflammatory, and anti-oxidant agent, which render it useful in addressing cardiovascular disease and some cancers. Scientists in Taiwan have found resveratrol to protect the BBB from the damaging effects of oxLDL attack on its tight junctions and the substances responsible for its integrity. (Lin. 2010)  (Chang. 2011)  In normal aging the BBB seems to remain intact, but its permeability becomes an issue. Certain drugs and physical conditions, such as hypertension, may have deleterious effects on its stability. The reactive oxygen species (ROS) spawned by these vehicles can be attenuated by a low molecular weight substance known as alpha-lipoic acid, a sulfurated fatty acid (a thiol) regarded as a member of the B vitamin family and used to metabolize carbohydrates. One of lipoic acid’s claims to fame is the capability to regenerate and to recirculate both the fat-soluble vitamin E and the water-soluble vitamin C, while simultaneously raising intracellular glutathione levels. In this regard it was cited as a meaningful tool in the treatment of oxidative brain damage and neural disorders involving free radicals, such as would arise from ischemia, excitotoxic amino acid brain insult, mitochondrial dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism and other causes of neural damage. What is deemed the most important thiol anti-oxidant, glutathione, is not usually directly administered, whereas alpha-lipoic acid may be. (Packer. 1997)   Analysis of studies on alpha-lipoic acid finds it to be a participant in processes of cell growth and differentiation, thus adding to its moniker, anti-oxidant of anti-oxidants. (Bilska. 2005)

No mention of anti-oxidants would be complete without vitamin C, the oxidized version of which—dehydroascorbic acid—can cross the BBB via glucose transporters. Though best known for its anti-oxidant powers, vitamin C is also involved in enzyme reactions and the manufacture of collagen in conjunction with amino acids. Because it can traverse the BBB, vitamin C (ascorbic acid) has welcome anti-oxidant potential in the central nervous system. (Agus. 1997). Its use in the treatment of cerebral compression insult, as from a concussion, has preserved BBB integrity and rescued somatosensory function from debilitation. (Lin. 2010)

For years, the failures of clinical trials in the treatment of neurological diseases have been blamed on the tested substances’ ineffectiveness, when the whole time none could get past the blood-brain barrier.


Abdul Muneer PM, Alikunju S, Szlachetka AM, Haorah J.
Inhibitory effects of alcohol on glucose transport across the blood-brain barrier leads to neurodegeneration: preventive role of acetyl-L: -carnitine.
Psychopharmacology (Berl). 2011 Apr;214(3):707-18. Epub 2010 Nov 16.

Abraham Al Ahmad, Carole Bürgi Taboada, Max Gassmann and Omolara O Ogunshola
Astrocytes and pericytes differentially modulate blood–brain barrier characteristics during development and hypoxic insult
Journal of Cerebral Blood Flow & Metabolism 31, 693-705 (February 2011) |

D B Agus, S S Gambhir, W M Pardridge, C Spielholz, J Baselga, J C Vera and D W Golde
Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters.
J Clin Invest.(December 1, 1997);100(11):2842–2848.

Beaumont A, Marmarou A, Fatouros P, Corwin F.
Secondary insults worsen blood brain barrier dysfunction assessed by MRI in cerebral contusion.
Acta Neurochir Suppl. 2002;81:217-9.

Bilska A, Włodek L.
Lipoic acid – the drug of the future?
Pharmacol Rep. 2005 Sep-Oct;57(5):570-7.

Carman Aaron J, Jeffrey H. Mills, Antje Krenz, Do-Geun Kim, and Margaret S. Bynoe
Adenosine Receptor Signaling Modulates Permeability of the Blood–Brain Barrier
The Journal of Neuroscience, 14 September 2011, 31(37): 13272-13280

Chang HC, Chen TG, Tai YT, Chen TL, Chiu WT, Chen RM.
Resveratrol attenuates oxidized LDL-evoked Lox-1 signaling and consequently protects against apoptotic insults to cerebrovascular endothelial cells.
J Cereb Blood Flow Metab. 2011 Mar;31(3):842-54.

Chen TG, Chen TL, Chang HC, Tai YT, Cherng YG, Chang YT, Chen RM.
Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway.
Toxicol Appl Pharmacol. 2007 Feb 15;219(1):42-53.

Chen X, Gawryluk JW, Wagener JF, Ghribi O, Geiger JD
Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer’s disease.
J Neuroinflammation. (1) 2008 Apr 3;5:12.

Chen X, Lan X, Roche I, Liu R, Geiger JD.
Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum.
J Neurochem. (2) 2008 Nov;107(4):1147-57.

Chen X, Ghribi O, Geiger JD
Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer’s and Parkinson’s diseases.
J Alzheimers Dis. 2010;20 Suppl 1:S127-41.

Garbuzova-Davis S, Louis MK, Haller EM, Derasari HM, Rawls AE, Sanberg PR.
Blood-brain barrier impairment in an animal model of MPS III B.
PLoS One. 2011 Mar 7;6(3):e16601.

Haorah J, Knipe B, Gorantla S, Zheng J, Persidsky Y.
Alcohol-induced blood-brain barrier dysfunction is mediated via inositol 1,4,5-triphosphate receptor (IP3R)-gated intracellular calcium release.
J Neurochem. 2007 Jan;100(2):324-36.

Kim HJ, Rowe M, Ren M, Hong JS, Chen PS, Chuang DM.
Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action.
J Pharmacol Exp Ther. 2007 Jun;321(3):892-901.

Lin JL, Huang YH, Shen YC, Huang HC, Liu PH.
Ascorbic acid prevents blood-brain barrier disruption and sensory deficit caused by sustained compression of primary somatosensory cortex.
J Cereb Blood Flow Metab. 2010 Jun;30(6):1121-36.

Lin YL, Chang HC, Chen TL, Chang JH, Chiu WT, Lin JW, Chen RM.
Resveratrol protects against oxidized LDL-induced breakage of the blood-brain barrier by lessening disruption of tight junctions and apoptotic insults to mouse cerebrovascular endothelial cells.
J Nutr. 2010 Dec;140(12):2187-92.

Mishra S, Palanivelu K.
The effect of curcumin (turmeric) on Alzheimer’s disease: An overview.
Ann Indian Acad Neurol 2008;11(1):13-19

Packer L, Tritschler HJ, Wessel K.
Neuroprotection by the metabolic antioxidant alpha-lipoic acid.
Free Radic Biol Med. 1997;22(1-2):359-78.

William M. Pardridge, MD
Targeting Neurotherapeutic Agents Through the Blood-Brain Barrier
Arch Neurol. 2002;59:35-40.

Rupprecht TA, Koedel U, Fingerle V, Pfister HW.
The pathogenesis of lyme neuroborreliosis: from infection to inflammation.
Mol Med. 2008 Mar-Apr;14(3-4):205-12.

Shah GN, Mooradian AD.
Age-related changes in the blood-brain barrier.
Exp Gerontol. 1997 Jul-Oct;32(4-5):501-19.

Spittle B.
Psychopharmacology of fluoride: a review.
Int Clin Psychopharmacol. 1994 Summer;9(2):79-82.

U.S. Dept. of Health and Human Services
Research Portfolio Online Reporting Tool, 2009

Q Xiang , Y Liang , L Chen , C Wang , B Chen), X Chen , M Zhou
Effect of fluoride in drinking water on children’s intelligence.
Fluoride 2003; 36(2): 84-94

Zhai JX, Guo ZY, Hu CL, Wang QN, Zhu QX.
Studies on fluoride concentration and cholinesterase activity in rat hippocampus.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2003 Apr;21(2):102-4.

Zhifei Wang, Yan Leng, Li-Kai Tsai, Peter Leeds and De-Maw Chuang
Valproic acid attenuates blood–brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition
Journal of Cerebral Blood Flow & Metabolism (2011) 31, 52–57

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Mighty Mitochondria… and Cardiolipin, Too

mitochondrion-cross-sectionMitochondria Are…

Suppose you were asked to name the most important part of your car?  Of course, without an engine you’re not going anywhere.  Without a transmission you’re not going anywhere, either.  So, which is it, the engine or the transmission?  Then, once you get moving, it’s nice to be able to stop.  Brakes, right?  Or perhaps you choose to steer around an obstacle.  Maybe there isn’t a most important part.  Ditto the cell, the unit of structure and function of living things, the smallest unit that can perform an essential life process.  Like your car, the cell has parts.  Considering that you have more than fifty trillion cells, the parts have to be tiny, really tiny.

Each cell is enclosed by a membrane that is made from proteins and a double layer of lipids.  The membrane is vital to the existence and function of the cell because it controls the flow of materials into and out of it, and it keeps the cell’s contents from spilling all over the place.  Not only does the cell have a membrane, but also do its components.  If we were to open and stretch out all the membranes of your body, they’d cover more than forty square miles.  But that’s nothing.  If we uncoiled all your strands of DNA and laid them end to end, they’d reach the sun and back more than once.  When the Psalmist said he was fearfully and wonderfully made, he didn’t realize how right he was.

A component of the cell that shares its architecture is the mitochondrion, sometimes referred to as the power plant of the cell because it makes most of the cell’s supply of adenosine triphosphate (ATP), used as a source of chemical energy.  Like the cell itself, the mitochondrion has an inner and an outer leaf to the membrane.  Mitochondria have other tasks besides making energy, including signaling, cell death, and control of the cell cycle. You already know that different cells have different jobs, each determined by what the nucleus says. Some cells do more work than others and require more energy.  Therefore, some have more mitochondria than others.  You would expect to find more mitochondria in a bicep than in the muscle that blinks an eye.  Each mitochondrion has an intermembrane space—found between the outer and inner membrane leaflets—that controls the movement of proteins. Small molecules have no problem crossing the outer membrane, but larger proteins need to be escorted by a specialized signaling sequence. (sorry about the alliteration)  A noted protein that is localized to the intermembrane area is called cytochrome c, the most abundant and stable cytochrome, principally involved in energy transfer.  Mitochondrial proteins vary depending on the tissue.  More than six hundred types have been identified in the human cardiac mitochondria, for example.  And, even though most of a cell’s DNA is in the nucleus, mitochondria have their own supply.

If there were no mitochondria, the higher animals could not exist.  Mitochondria perform aerobic respiration, requiring oxygen, which is the reason we breathe.  Without them we would have to rely on anaerobic respiration, without oxygen.  That process is too inefficient to support us.  Besides, the lack of mitochondria would reduce energy production by fifteen times, which is far too low to allow survival. A mitochondrion’s DNA reproduces independently of the cell in which it is found.  In humans, this DNA covers more than sixteen thousand base pairs, not very many compared to the whole organism.  Mitochondrial DNA holds thirty-seven genes, all of which are needed for normal function.  Thirteen of these supply information for making enzymes involved in oxidative phosphorylation, which is how ATP is made by using oxygen and simple sugars.  The other twenty-four genes help to make transfer RNA (tRNA) and ribosomal RNA (rRNA), which are chemically related to DNA.  These kinds of RNA are responsible for assembling amino acids into functioning proteins.

Mitochondria are passed on through maternal lineage.  Just as a car’s energy supply from gasoline is in the rear, so is a sperm’s mitochondrial energy—in the tail, which falls off after the sperm attaches to the egg.  This means that any problems, like mitochondrial diseases, necessarily come from the female.  Mitochondrial DNA (mtDNA) does not get shifted from generation to generation, while nuclear DNA does.  It is mtDNA that sends some diseases down the line.  mtDNA, though, is also subject to non-inherited mutations that cause diseases.  Fortunately, these are not passed on, but are accountable for various cancers, such as breast, colon, stomach and liver, diseases that have been attributed to reactive oxygen species.  mtDNA has limited capability to repair itself, so the inherited changes may cause problems with the body’s systems, where the mitochondria are unable to provide sufficient energy for cells to do their work.  The inherited consequences may present as muscle wasting, movement problems, diabetes, dementia, hearing loss, or a host of other maladies.

Some mitochondrial functions are performed only in specific cells.  In the liver, for example, they are able to detoxify ammonia, a job that need not be accomplished anywhere else in the body.  Other metabolic tasks of mitochondria include regulation of membrane potential, apoptosis, calcium signaling, steroid synthesis, and control of cellular metabolism.  You can see that mitochondria are vital to life, and their malfunction can change the rules.  In some mitochondrial dysfunctions there is an interaction of environmental and hereditary factors that causes disease.  Such may be the case with pesticides and the onset of Parkinson’s disease—cellular damage related to oxidative stress.  In other dysfunctions, there may be mutations of certain enzymes, such as coenzyme Q10 deficiency, or aberrations in the cardiolipin molecules that are found inside mitochondria, causative of Barth syndrome, which is often associated with cardiomyopathy.  Mitochondria-mediated oxidative stress may also play a role in Type 2 diabetes.  In cases where misconstrued fatty acid uptake by heart cells occurs, there is increased fatty acid oxidation, which upsets the electron transport chain, resulting in increased reactive oxygen species.  This deranges the mitochondria and elevates their oxygen consumption, resulting in augmentation of fatty acid oxidation.  Merely because oxygen consumption increases does not necessarily mean that more ATP will be manufactured, mostly because the mitochondria are uncoupled.  Less ATP ultimately causes energy deficit, accompanied by reduced cardiac efficiency.

Mitochondria can become involved in a vicious cycle of oxidative stress leading to mitochondrial DNA mutations, which leads to enzyme irregularities and more oxidative stress.  This may be a major factor in the aging process.

Rescue My Mitochondria, Please

The neurodegeneration of Parkinson’s disease is characterized by a loss of dopaminergic neurons and a deficit in mitochondrial respiration.  Exposure to some neurotoxins can present with both characteristics.  In a Parkinson’s model provoked by a drug that was produced to mimic the effects of morphine or meperidine (Demerol), but which interferes with oxidative phosphorylation in mitochondria instead, causing depletion of ATP and cell death, scientists at Columbia University’s Center for Neurobiology and Behavior found that the administration of ketone bodies akin to those used in the treatment of epilepsy were able to attenuate the dopaminergic neurodegeneration and motor deficits induced by the drug (Tieu, 2003).  From this and other studies it has been determined that ketones may play a therapeutic role in several forms of neurodegeneration related to mitochondrial dysfunction (Kashiwaya, 2000).

Moving across the mitochondrial membrane, phosphatidylcholine (PC) limits the phospholipid turnover in both the inner and outer leaflets that epitomizes the membrane defect identified in neurological diseases (Dolis, 1996), including Alzheimer’s, a disease in which impairment of mitochondrial function is part of the pathophysiology.  Substances that inhibit mitochondrial function also activate an enzyme called phospholipase A2 (PLA2) that degrades PC in the membrane (Farber, 2000), but reparation to mitochondria may be realized by administering PC liposomes, as evidenced by Russian studies performed in the early 1990s (Dobrynina, 1991).

Cardiolipin is an important component of the inner mitochondrial membrane, where it makes up about 20% of the lipid composition.  Its operational character is critical to the optimal function of numerous enzymes essential to mitochondrial energy metabolism.  Mitochondrial cardiolipin is distinguished from other phospholipids by the presence of linoleic acid derivatives (Schlame, 1990).  The formation of cardiolipin is dependent upon molecules donated by PC, but because it contains 18-carbon fatty alkyl chains with two unsaturated bonds, it bespeaks a linoleic acid heritage.   The need for linoleic acid, an omega-6 fat, was announced by the American Heart Association several years ago (Harris, 2009).

In the aforementioned Barth syndrome there exist cardiolipin abnormalities and resultant defects in the electron transport chain proteins and the architecture of the mitochondrion.   The electron transport chain (ETC) moves electrons from one cytochrome to another during the production of ATP, terminating at oxygen through a series of increasingly strong oxidative activities.  Those few electrons that fail to make it through the entire process leak and form superoxide, a substantially reactive molecule that contributes greatly to oxidative stress and aging.

Since the heart is rich in cardiolipin, it is more than appropriate to maintain its stores.  And linoleic acid is just the thing to do that.  Dutch researchers found that linoleic acid, readily available from sunflower, hemp, grape seed and other oils, restores and even increases cardiolipin levels (Valianpour, 2003).   Chronic over-consumption of omega-3 fats, such as those from fish oils, creates a deficit of omega-6 fats that interferes with the rate of oxygen use by mitochondria, with consequent decrease of cardiolipin (Yamaoka, 1999) (Hauff, 2006).

Coronary heart disease is a major health issue that may be addressed by supporting cardiolipin integrity, but other conditions likewise respond to such support.  Besides maintaining membrane potential and architecture, cardiolipin provides sustainment to several proteins involved in mitochondrial energy production.  If cardiolipin activity is interrupted or deranged, either through oxidative stress or alterations in acyl chain composition, we may anticipate contending with other pathological conditions, such as ischemia and hypothyroidism, and accelerated aging (Chicco, 2007).  These concerns can be allayed by attending to the status of the tafazzin protein that partly underlies cardiolipin metabolism (Xu, 2006).  Superheroes have long been associated with a sidekick, occasionally with role reversal for the nonce.  Working with linoleic acid to bolster cardiolipin is phosphatidylcholine (PC), which assists protein reconstitution by its ability to transfer acyl groups (Xu, 2003) (Schlame, 1991) and enhance protein signaling.  PC exists in every cell of the body, occupying the outer leaflet of the membrane.  Throughout the course of life, PC levels become depleted and may drop as low as 10% of the membrane in elderly people.  Being so, supplementation is warranted, not only to maintain cardiolipin levels and mitochondrial stability body-wide, but also to retard senescence and to improve brain function and memory capacity.


Ardail D, Privat JP, Egret-Charlier M, Levrat C, Lerme F, Louisot P.
Mitochondrial contact sites. Lipid composition and dynamics.
J Biol Chem. 1990 Nov 5;265(31):18797-802.

Chicco AJ, Sparagna GC.
Role of cardiolipin alterations in mitochondrial dysfunction and disease.
Am J Physiol Cell Physiol. 2007 Jan;292(1):C33-44. Epub 2006 Aug 9.

Chung SY, Moriyama T, Uezu E, Uezu K, Hirata R, Yohena N, Masuda Y, Kokubu T, Yamamoto S.
Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia.
J Nutr. 1995 Jun;125(6):1484-9.

Dobrynina OV, Migushina VL, Shatinina SZ, Kapitanov AB.
 [Reparation of hepatocyte mitochondrial membranes using phosphatidylcholine liposomes].
Biull Eksp Biol Med. 1991 Aug;112(8):135-6.

Danièle Dolis, Anton I. P. M. de Kroon and Ben de Kruijff
Transmembrane Movement of Phosphatidylcholine in Mitochondrial Outer Membrane Vesicles
The Journal of Biological Chemistry. May 17, 1996; 271: 11879-11883.

John R. Dyer, Carol E. Greenwood
The level of linoleic acid in neural cardiolipin is linearly correlated to the amount of essential fatty acids in the diet of the weanling rat
The Journal of Nutritional Biochemistry. Vol 2, Iss 9, Sept 1991, Pages 477–483

Acceleration of phosphatidylcholine synthesis and breakdown by inhibitors of mitochondrial function in neuronal cells: a model of the membrane defect of Alzheimer’s disease
The FASEB Journal. November 1, 2000; vol. 14 no. 14: 2198-2206

Haines, Thomas H.
A New Look at Cardiolipin (Editorial)
Biochimica et Biophysica Acta 1788 (2009): 1997-2001

Hauff KD, Hatch GM.
Cardiolipin metabolism and Barth Syndrome.
Prog Lipid Res. 2006 Mar;45(2):91-101. Epub 2006 Jan 18.

Houtkooper RH, Vaz FM.
Cardiolipin, the heart of mitochondrial metabolism.
Cell Mol Life Sci. 2008 Aug;65(16):2493-506.

Hovius R, Thijssen J, van der Linden P, Nicolay K, de Kruijff B.
Phospholipid asymmetry of the outer membrane of rat liver mitochondria. Evidence for the presence of cardiolipin on the outside of the outer membrane.
FEBS Lett. 1993 Sep 6;330(1):71-6.

Hung MC, Shibasaki K, Yoshida R, Sato M, Imaizumi K.
Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine-vitamin B12 diet.
Br J Nutr. 2001 Aug;86(2):163-71.

Kulik W, van Lenthe H, Stet FS, Houtkooper RH, Kemp H, Stone JE, Steward CG, Wanders RJ, Vaz FM.
Bloodspot assay using HPLC-tandem mass spectrometry for detection of Barth syndrome.
Clin Chem. 2008 Feb;54(2):371-8. Epub 2007 Dec 10.

Ho-Joo Lee, Jana Mayette, Stanley I Rapoport and Richard P Bazinet
Selective remodeling of cardiolipin fatty acids in the aged rat heart
Lipids in Health and Disease. 23 January 2006; 5:2

F. B. Jungalwala, R. M. C. Dawson
The Origin of Mitochondrial Phosphatidylcholine within the Liver Cell
European Journal of Biochemistry. Volume 12, Issue 2, pages 399–402, February 1970

Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL.
D-beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease.
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5440-4.

Nicolay K, Hovius R, Bron R, Wirtz K, de Kruijff B.
The phosphatidylcholine-transfer protein catalyzed import of phosphatidylcholine into isolated rat liver mitochondria.
Biochim Biophys Acta. 1990 Jun 11;1025(1):49-59.

Paradies G, Petrosillo G, Paradies V, Ruggiero FM.
Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease.
Cell Calcium. 2009 Jun;45(6):643-50. Epub 2009 Apr 15.

José L. Quiles, Estrella Martínez, Susana Ibáñez, Julio J. Ochoa, Yolanda Martín, Magdalena López-Frías, Jesús R. Huertas and José Mataix
Ageing-Related Tissue-Specific Alterations in Mitochondrial Composition and Function Are Modulated by Dietary Fat Type in the Rat
Journal of Bioenergetics and Biomembranes . Volume 34, Number 6 (2002), 517-524

Schlame M, Rüstow B.
Lysocardiolipin formation and reacylation in isolated rat liver mitochondria.
Biochem J. 1990 Dec 15;272(3):589-95

Schlame M, Beyer K, Hayer-Hartl M, Klingenberg M.
Molecular species of cardiolipin in relation to other mitochondrial phospholipids. Is there an acyl specificity of the interaction between cardiolipin and the ADP/ATP carrier?
Eur J Biochem. 1991 Jul 15;199(2):459-66.

Sparagna GC, Lesnefsky EJ.
Cardiolipin remodeling in the heart.
J Cardiovasc Pharmacol. 2009 Apr;53(4):290-301

Nicole Testerink , Michiel H. M. van der Sanden , Martin Houweling , J. Bernd Helms, and
Arie B. Vaandrager
Depletion of phosphatidylcholine affects endoplasmic reticulum morphology and protein traffi c at the Golgi complex
J. Lipid Res. 2009. 50: 2182–2192.

Kim Tieu, Celine Perier, Casper Caspersen, Peter Teismann, Du-Chu Wu, Shi-Du Yan, Ali Naini, Miquel Vil, Vernice Jackson-Lewis, Ravichandran Ramasamy and Serge Przedborski
D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease

J Clin Invest. Sept 15, 2003; 112(6):892–901.

Trivedi A, Fantin DJ, Tustanoff ER.
Role of phospholipid fatty acids on the kinetics of high and low affinity sites of cytochrome c oxidase.
Biochem Cell Biol. 1986 Nov;64(11):1195-210.

Valianpour F, Wanders RJ, Overmars H, Vaz FM, Barth PG, van Gennip AH.
Linoleic acid supplementation of Barth syndrome fibroblasts restores cardiolipin levels: implications for treatment.
J Lipid Res. 2003 Mar;44(3):560-6. Epub 2002 Dec 16.

Vance JE.
Phospholipid synthesis in a membrane fraction associated with mitochondria.
J Biol Chem. 1990 May 5;265(13):7248-56.

Wright MM, Howe AG, Zaremberg V
Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues.
Biochem Cell Biol. 2004 Feb;82(1):18-26.

Xu Y, Kelley RI, Blanck TJ, Schlame M.
Remodeling of cardiolipin by phospholipid transacylation.
J Biol Chem. 2003 Dec 19;278(51):51380-5. Epub 2003 Oct 9.

Xu Y, Malhotra A, Ren M, Schlame M.
The enzymatic function of tafazzin.
J Biol Chem. 2006 Dec 22;281(51):39217-24. Epub 2006 Nov 2.

Yamaoka S, Urade R, Kito M.
Cardiolipin molecular species in rat heart mitochondria are sensitive to essential fatty acid-deficient dietary lipids.
J Nutr. 1990 May;120(5):415-21.

Zeisel SH.
Dietary choline deficiency causes DNA strand breaks and alters epigenetic marks on DNA and histones.
Mutat Res. 2011 Oct 20. [Epub ahead of print]

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Gut Health, Body Health

stomachThe large intestine is seldom the topic of conversation, with the possible exception of surgeons and gastroenterologists. Most “civilians” don’t pay attention to it until it isn’t working right. The inability to move material out of it is one reason. Unusual egesta might be another. Regardless of its laid back persona, the colon is actually an interesting character. It runs from the cecum (the beginning of the large intestine, where the appendix hangs) to the rectum (the dumpster), and extends about five or six feet. If you want to be technical, the colon runs between these two points. The large intestine has no digestive function, but lubricates wastes and absorbs water and remaining salts, and stores useless stuff for eventual removal. It takes about sixteen hours to evacuate the hold. You need to know that the large intestine absorbs vitamins made by colonic bacteria, such as vitamin K and the vitamin A converted from beta-carotene.

Despite that the colon is known for removal of material, there exists inside a raft of bacteria that keep a permanent residence. In fact, there are more bacteria in the colon than cells in the body. If you have ten trillion cells in your body, you have ten times that many microbes, weighing from two to five pounds. This microflora is sometimes called the microbiome or microbiota. Whichever term is used, the activities performed by these bacteria parallel that of an organ, rivaling the metabolic capacity of the liver (MacFarlane, 2010). For example, carbohydrates are fermented to form short-chain fatty acids that support epithelial cell growth, which helps to reduce the absorption of toxic products. The flora recycle carbon and nitrogen, manufacture methane, metabolize steroids, convert lignans and phytoestrogens to other compounds and fight invasion by unwelcome species. Although people can survive without them, these bacteria are among the best of friends. Damaged or abnormal gut flora is the cause of much human agony as a prime factor in disease. Treating the microbiome with dignity and respect may prevent, or even reverse, disorders that include heart disease, autoimmune conditions, allergies and cancer (deVrese, 2008) (Garcovich, 2012).

There are hundreds of different species of micro-organisms living in the gut, more than 95% of which are anaerobic and genetically diverse. A lactobacillus is more different from a bifidobacterium than a human is from a rabbit. Identification of all species is difficult because not all can be cultured, but you can rest assured that your bacteria belong to you, remaining fairly constant throughout your life time. Talk about close friends!  The healthy bacteria provide a natural barrier against pathogenic bacteria, parasites, fungi, viruses, toxins and whatever else would wreak havoc with our health. Basically, there are half a dozen main groups:  Bacteroides, Firmicutes (Clostridia, Lactobacilli, Streptococci), Actinobacteria (Bifido-), Proteobacteria (Entero-), Fusobacteria and Verrucomicrobia. Not all of these offer salubrity. Some are so complex they almost defy taxonomy, but to our benefit, the good control the evil (Vedantam, 2003) (Beaugerie, 2004).

Analyses have determined that specific gut microbes are associated with what we eat. Some are associated with carbohydrates and some with animal proteins, fats and amino acids. It appears they come to the front of the class when it’s their turn to perform. Changing diet from one type of macro-nutrient to another can alter which bacterial strain is on stage at the time. A baby’s gut is clean and sterile until it entertains bacteria from its mother. Vaginal birth may afford bacterial strains directly from mom’s gastrointestinal tract, while caesarean might present strains from the ambient environs, including the air and the attending medical folks. The infant doesn’t establish his own microbiota for up to six months after caesarean delivery, only one month for normal birth. In any case, the microbiota shapes the development of the immune system, and the immune system in turn shapes the composition of the microbiota (Nicholson, 2012).

The influence of gut microbes on immunity is profound and, therefore, associated with long-term health, particularly since microflora is relatively stable throughout adulthood. The dynamics of the gut environment are subject to perturbations, though, such as from stresses or dietary changes. It’s comforting to know that there is considerable interest in developing modalities that can manipulate biome composition to benefit the host through a kind of metabolic communication, such as would affect obesity and type 2 diabetes (Kootte, 2012). In these matters, therapeutic pathways may be designed by enlisting short-chain fatty acids, prebiotics, bile acids and probiotics. Realizing that antibiotics are non-selective in destroying bacteria—they kill the good as well as the bad—this give us the means for resolution of myriad complaints. In general, the host immune system can prevent the overgrowth of pathogens, which, upon ingestion, fall to this complex integrated structure.

Probiotics are helpful in many cases, but are not silver bullets. When used as part of a broad nutritional protocol, they are likely effective in establishing or re-establishing a healthy microbiome. Stress management, elimination of detrimental medications and dietary interventions need to be included in such a protocol. Because they are many and varied in their composition, probiotics are often viewed tentatively until they are administered and monitored for efficacy. Eating fermented foods, like sauerkraut, yogurt and kefir, fosters a nurturing environment for your own microbiome. The florae best known are the Lactobacilli (there are more than 50 strains) and Bifidobacteria (there are more than thirty). Lacto-, in one strain or another, have been used to treat and to prevent a variety of conditions, from bacterial vaginosis to childhood abdominal distress and diarrhea, to childhood respiratory infections. Bifidobacteria comprise about 90% of the intestinal community, and appear in an infant’s gut within days of parturition, especially if breastfed. The Bifido- species has been used to address irritable bowel syndrome, dental caries, blood lipids and glucose tolerance.  A knowledgeable nutrition professional can guide you in the choice of probiotics to meet a specific need if you have one. Oh, yeah, there is a yeast probiotic, called Saccharomyces boulardii, which is quite effective in treating diarrhea associated with antibiotic use, and may even be helpful with Clostridium difficile and acne.

Hey, what about short-chain fatty acids (SCFA), especially butyrate?  We’re glad you asked. Butyrate is derived from the bacterial fermentation of resistant starches and fibers. Its multiple beneficial effects have been demonstrated beyond the colon, mostly because SCFA can be absorbed across the colonic epithelium. Now that gut health has its own fan club, what with renewed interest in the GI barrier defense system, SCFAs are the darlings of moneyed research. These 2-carbons to 5-carbons fatty acids include acetate, propionate, butyrate and valerate, but the 4-carbon butyrate is the featured performer due to its multiplicity of virtues. Among butyrate’s mechanisms of action are the regulation of gene expression, inhibition of histone deacetylase (an action which helps to make copies of DNA), sequestration of ammonia (ammonia causes cloudy thinking), mobilization of renegade fats, and clearance of biotoxins (Soret, 2010) (Fusunyan, 1999) (Yin, 2001). Because butyrate availability in the colon is lower than the other SCFAs, supplementation is highly recommended. You can’t eat enough resistant starches to make enough butyrate to be physiologically significant. However, even at low concentrations, butyrate can inhibit cell proliferation of several colon cancer lines. At high concentrations, it works like gangbusters against cancer cells while leaving healthy cells alone (Omaida, 1996) (Gamet, 1992).

The extraordinary complexity of the human microbiome is only recently revealed, despite having been known for decades. The interdependence between beneficial bacteria and the immune system demands recognition. If the florae can fight the inflammation that threatens them, they can fight whatever threatens their host.


Arora T, Sharma R, Frost G.
Propionate. Anti-obesity and satiety enhancing factor?
Appetite. 2011 Apr;56(2):511-5. doi: 10.1016/j.appet.2011.01.016. Epub 2011 Jan 19.

Bäckhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, Versalovic J, Young V, Finlay BB.
Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications.
Cell Host Microbe. 2012 Nov 15;12(5):611-22.

Beaugerie L, Petit JC.
Microbial-gut interactions in health and disease. Antibiotic-associated diarrhoea.
Best Pract Res Clin Gastroenterol. 2004 Apr;18(2):337-52.

Bischoff SC.
‘Gut health’: a new objective in medicine?
BMC Med. 2011 Mar 14;9:24.

Calder PC, Krauss-Etschmann S, de Jong EC, Dupont C, Frick JS, Frokiaer H, Heinrich J, Garn H, et al
Early nutrition and immunity – progress and perspectives.
Br J Nutr. 2006 Oct;96(4):774-90.

Roberto Berni Canani, Margherita Di Costanzo, and Ludovica Leone
The epigenetic effects of butyrate: potential therapeutic implications for clinical practice
Clin Epigenetics. 2012; 4(1): 4.

Cummings JH, Antoine JM, Azpiroz F, Bourdet-Sicard R, Brandtzaeg P, Calder PC, Gibson GR, et al
PASSCLAIM–gut health and immunity.
Eur J Nutr. 2004 Jun;43 Suppl 2:II118-II173.

de Vrese M, Schrezenmeir J.
Probiotics, prebiotics, and synbiotics.
Adv Biochem Eng Biotechnol. 2008;111:1-66. doi: 10.1007/10_2008_097.

Fanaro S, Chierici R, Guerrini P, Vigi V.
Intestinal microflora in early infancy: composition and development
Acta Paediatr Suppl. 441: 48-55. 2003

Flint HJ, Scott KP, Louis P, Duncan SH.
The role of the gut microbiota in nutrition and health.
Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):577-89.

Fusunyan RD, Quinn JJ, Fujimoto M, MacDermott RP, Sanderson IR.
Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation.
Mol Med. 1999 Sep;5(9):631-40.

Gamet L, Daviaud D, Denis-Pouxviel C, Remesy C, Murat JC.
Effects of short-chain fatty acids on growth and differentiation of the human colon-cancer cell line HT29.
Int J Cancer. 1992 Sep 9;52(2):286-9.

Garcovich M, Zocco MA, Roccarina D, Ponziani FR, Gasbarrini A.
Prevention and treatment of hepatic encephalopathy: Focusing on gut microbiota.
World J Gastroenterol. 2012 Dec 14;18(46):6693-700. doi: 10.3748/wjg.v18.i46.6693.

Guarner F, Malagelada JR.
Gut flora in health and disease.
Lancet. 2003 Feb 8;361(9356):512-9.

Kootte RS, Vrieze A, Holleman F, Dallinga-Thie GM, Zoetendal EG, de Vos WM, Groen AK, et al
The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus.
Diabetes Obes Metab. 2012 Feb;14(2):112-20.

Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ
Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms.
PLoS One. 2012;7(4):e35240. doi: 10.1371/journal.pone.0035240. Epub 2012 Apr 10.

Macfarlane S, Macfarlane GT.
Regulation of short-chain fatty acid production.
Proc Nutr Soc. 2003 Feb;62(1):67-72.

MacFarlane, George T. and McBain, Andrew J. (2010). The Human Colonic Microbiota. In Colonic Microbiota, Nutrition and Health. Glenn Gibson, Ed. Dordrecht, the Netherlands: Kluwer Academic Publishers; pp 1-25

Martin FP, Dumas ME, Wang Y, Legido-Quigley C, Yap IK, Tang H, Zirah S, Murphy GM, et al
A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model.
Mol Syst Biol. 2007;3:112.

Martin FP, Wang Y, Sprenger N, Yap IK, Lundstedt T, Lek P, Rezzi S, Ramadan Z, van Bladeren P, et al
Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model.
Mol Syst Biol. 2008;4:157.

Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S.
Host-gut microbiota metabolic interactions.
Science. 2012 Jun 8;336(6086):1262-7.

O’Hara AM, Shanahan F.
The gut flora as a forgotten organ.
EMBO Rep. 2006 Jul;7(7):688-93.

Omaida C. Velázquez MD, Howard M. Lederer MD, Dr. John L. Rombeau MD
Butyrate and the colonocyte
Digestive Diseases and Sciences. April 1996, Volume 41, Issue 4, pp 727-739

Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, Wolvers D, Watzl B, et al
Prebiotic effects: metabolic and health benefits.
Br J Nutr. 2010 Aug;104 Suppl 2:S1-63.

Schwiertz A, Gruhl B, Löbnitz M, Michel P, Radke M, Blaut M.
Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants.
Pediatr Res. 2003 Sep;54(3):393-9. Epub 2003 Jun 4.

Scott KP, Duncan SH, Louis P, Flint HJ.
Nutritional influences on the gut microbiota and the consequences for gastrointestinal health.
Biochem Soc Trans. 2011 Aug;39(4):1073-8.

Scott KP, Gratz SW, Sheridan PO, Flint HJ, Duncan SH.
The influence of diet on the gut microbiota.
Pharmacol Res. 2012 Nov 9. pii: S1043-6618(12)00207-1.

Soret R, Chevalier J, De Coppet P, Poupeau G, Derkinderen P, Segain JP, Neunlist M.
Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats.
Gastroenterology. 2010 May;138(5):1772-82.

Tsai F, Coyle WJ.
The microbiome and obesity: is obesity linked to our gut flora?
Curr Gastroenterol Rep. 2009 Aug;11(4):307-13.

Vedantam G, Hecht DW.
Antibiotics and anaerobes of gut origin.
Curr Opin Microbiol. 2003 Oct;6(5):457-61.

Yin L, Laevsky G, Giardina C.
Butyrate suppression of colonocyte NF-kappa B activation and cellular proteasome activity.
J Biol Chem. 2001 Nov 30;276(48):44641-6. Epub 2001 Sep 25.

Yonezawa H, Osaki T, Hanawa T, Kurata S, Zaman C, Woo TD, Takahashi M, Matsubara S, Kawakami H, Ochiai K, Kamiya S.
Destructive effects of butyrate on the cell envelope of Helicobacter pylori.
J Med Microbiol. 2012 Apr;61(Pt 4):582-9.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Colon and Butyrate: The Colon Beyond Punctuation

crammed-jarQuite a lot of people do not like to share their space. It’s understandable that some are uncomfortable when a conversation, as with a stranger, is carried on nose to nose. In Arab countries, it is offensive to step or lean away during such an encounter. There is, however, an instance where closeness cannot be avoided with the microbiome that occupies not only our space, but also us. The human body holds ten times more microbes than human cells, some on the outside, and others on the inside. The skin, the largest organ of the body, houses a range of microbes that live in distinct communities yet work together to protect us from attack by sickness and disease (Grice, 2009). But our attention here is to those on the inside, the microbiota that weigh up to three pounds and contain tens of trillions of members. There might even be more than a thousand different species, about a third of which are common to most of us. The other two-thirds belong only to you.

Though we have a tailor-made personal microbiome, all perform the same physiological functions and have a direct impact on our health. Besides completing digestion by absorbing water and storing wastes, the gut microbes help to make biotin and vitamin K while fighting aggression from the pathogenic gang of bugs and bolstering the immune system. Each of our gut communities remains stable throughout our lives, unless dietary changes are dramatic. Those who consume lots of vegetables and fiber have a different composition from those who live on fatty meats and simple carbohydrates. What happens in the gut telegraphs to what happens in other areas of the body, including areas that manage mood and possibly the onset of chronic and degenerative diseases (Tillisch, 2013).

The neonatal biome starts to form right after birth, when the digestive tract becomes colonized by micro-organisms that come from the mother and from the environment into which it is born. In about three years the biome becomes stable. To keep it that way, we need to take measures that transcend dietary behavior and the mere swallowing of probiotics as adults. Probiotics are micro-organisms. To analogize, they’re like police whose local precinct needs a workplace conducive to efficiency.  If a probiotic, or any array of gut bacteria for that matter, is to augment or to enhance the native population, it needs a favorable place to work. The problem with the typical Western diet is that we feed the upper GI tract without feeding the gut. One way to do that is with resistant starch, the fermentation of which manufactures short-chain fatty acids, notably butyrate. Butyrate nourishes the gut barrier and helps to prevent inflammation.  Very often, however, dietary intake of resistant starch is insufficient to make enough butyrate to be physiologically significant.

What does butyrate do?  It has powerful effects on several colonic functions, not the least of which is the inhibition of inflammation and carcinogenesis, and the reinforcement of the defenses that fight infection and oxidative stress (Hamer, 2008). Butyrate has partners and precursors in the form of acetates and propionates, likewise made by the bacterial fermentation of resistant starch and fiber.  In the company of acetate, butyrate is reported to protect against diet-induced obesity without causing hypophagia, while propionate may reduce food intake. Unfortunately, there is little understanding why this works (Hua, 2012). What distinguishes one from another?  The number of carbons it holds. Acetic acid has two, propionic acid has three and butyric acid has four. The first of these has the scent of vinegar. Propionic acid is found in sweat; butyric acid in rancid butter and vomit.

Butyrate, joined with calcium, magnesium, potassium, sodium or a combination of these minerals inhibits histone deacetylase enzymes, helping butyric acid to enhance the transcription activity of DNA. Sodium butyrate, for example, has been found to increase lifespan in animal experiments (Zhang, 2009). Of the three short-chain fatty acids mentioned, butyrate is more potent than the others at inhibiting invasive colon cancers (Emenaker, 1998). If this activity of the butyrate molecule has been known since the late 1990’s, why has it not received the publicity that newly-concocted drugs, with their hosts of nasty side effects, have?

The reasons for paying attention to your gut go beyond what you read while seated. Some problems can be attenuated with an occasional laxative, although increasing dietary fiber is a better technique. Even the orange-flavored stuff in the plastic canister, used every day, is an improvement. But a butyrate supplement, despite its pungency, is the best thing going, especially as we get older.


Arora T, Sharma R, Frost G.
Propionate. Anti-obesity and satiety enhancing factor?
Appetite. 2011 Apr;56(2):511-5.

Bergman EN.
Energy contributions of volatile fatty acids from the gastrointestinal tract in various species.
Physiol Rev. 1990 Apr;70(2):567-90.

Roberto Berni Canani, Margherita Di Costanzo, Ludovica Leone, Monica Pedata, Rosaria Meli, and Antonio Calignano
Potential beneficial effects of butyrate in intestinal and extraintestinal diseases
World J Gastroenterol. Mar 28, 2011; 17(12): 1519–1528.

Emenaker NJ, Basson MD.
Short chain fatty acids inhibit human (SW1116) colon cancer cell invasion by reducing urokinase plasminogen activator activity and stimulating TIMP-1 and TIMP-2 activities, rather than via MMP modulation.
J Surg Res. 1998 Apr;76(1):41-6.

Galvez J, Rodriguez-Cabezas ME, Zarzuelo A.
Effects of dietary fiber on inflammatory bowel disease.
Mol Nutr Food Res. 2005 Jun;49(6):601-8.

Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, Cefalu WT, Ye J.
Butyrate improves insulin sensitivity and increases energy expenditure in mice.
Diabetes. 2009 Jul;58(7):1509-17.

Grice EA, Kong HH, Conlan S, Deming CB, Davis J, Young AC; NISC Comparative Sequencing Program, Bouffard GG, Blakesley RW, Murray PR, Green ED, Turner ML, Segre JA.
Topographical and temporal diversity of the human skin microbiome.
Science. 2009 May 29;324(5931):1190-2.

Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ.
Review article: the role of butyrate on colonic function.
Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19.

Hua V. Lin, Andrea Frassetto, Edward J. Kowalik Jr, Andrea R. Nawrocki, Mofei M. Lu,
Jennifer R. Kosinski, James A. Hubert, Daphne Szeto, Xiaorui Yao, Gail Forrest, Donald J. Marsh
Butyrate and Propionate Protect against Diet-Induced Obesity and Regulate Gut Hormones via Free Fatty Acid Receptor 3-Independent Mechanisms
PLoS ONE. April 10, 2012 7(4): e35240. doi:10.1371/journal.pone.0035240

Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI.
Human nutrition, the gut microbiome and the immune system.
Nature. 2011 Jun 15;474(7351):327-36. doi: 10.1038/nature10213.

Arya Khosravi, Alberto Y—ez, Jeremy G. Price, Andrew Chow, Miriam Merad, Helen S. Goodridge, Sarkis K. Mazmanian
Gut Microbiota Promote Hematopoiesis to Control Bacterial Infection
Cell Host and Microbe. Volume 15, Issue 3, Pages 374-381 (12 March 2014)

Lewis SJ, Heaton KW.
Increasing butyrate concentration in the distal colon by accelerating intestinal transit.
Gut. 1997 Aug;41(2):245-51.

Mortensen PB, Clausen MR.
Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease.
Scand J Gastroenterol Suppl. 1996;216:132-48.

Sakakibara S, Yamauchi T, Oshima Y, Tsukamoto Y, Kadowaki T.
Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice.
Biochem Biophys Res Commun. 2006 Jun 2;344(2):597-604.

Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ.
Colonic health: fermentation and short chain fatty acids.
J Clin Gastroenterol. 2006 Mar;40(3):235-43.

Zhang M, Poplawski M, Yen K, Cheng H, Bloss E, Zhu X, Patel H, Mobbs CV.
Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling.
PLoS Biol. 2009 Nov;7(11):e1000245.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.